Dopamine Cytotoxicity Involves Both Oxidative and Nonoxidative Pathways in SH-SY5Y Cells: Potential Role of Alpha-Synuclein Overexpression and Proteasomal Inhibition in the Etiopathogenesis of Parkinson's Disease
Figure 9
Probable mechanisms of dopamine cytotoxicity in SH-SY5Y cells: involvement of alpha-synuclein and proteasomal inhibition. (a) shows that dopamine causes cell death and mitochondrial dysfunctions involving both the oxidative (NAC responsive) and nonoxidative (NAC nonresponsive) mechanisms. (b) shows that dopamine causes proteasomal inhibition and increased alpha-synuclein gene expression involving similar kind of oxidative (NAC responsive) and nonoxidative (NAC nonresponsive) mechanisms. Both of these effects cause increased intracellular accumulation of alpha-synuclein. (c) shows our “proteasomal inhibition model’’ using lactacystin resulting in cell death, mitochondrial dysfunctions, and increased intracellular alpha-synuclein accumulation.
